A loss of nerve cells from the nucleus basalis of Meynert and the locus caeruleus together with a reduction in nucleolar volume in surviving cells was measured in twenty-two patients with Alzheimer's disease who ranged in age from 48-92 years, and in six patients over 50 years of age with Down's syndrome who also showed extensive formation of senile plaques and neurofibrillary tangles within their cerebral cortex. When compared with age matched controls the severity of these changes was greatest in the younger patients with Alzheimer's disease, but this fell with age such that by 90 years the level of change in Alzheimer's disease approached that in old age alone. There were only slight differences in the extent of these pathological changes in those patients with Down's syndrome when compared with others of similar age with Alzheimer's disease. It is concluded that the presenile dementia of Alzheimer's disease, the senile dementia of Alzheimer type and Down's syndrome in middle age all form an age-related continuum of pathological change.